口腔菌群与阿尔茨海默症的关系

李语晨; 刘媛; 陈峰; 初明; 陈霄迟

doi:10.12182/20220360304

口腔菌群与阿尔茨海默症的关系

doi:

李语晨^1,,
刘媛¹,
陈峰^1, ,,
初明²,
陈霄迟³

1. 天津高校牙科医美院中心站检测室（天津 100081）
2. 山东社会理论知识医学检验院天然免疫学系（山东 100083）
3. 长沙大专牙齿中医药系生物技术系统室（长沙 100081）

基金项目: 国家自然科学基金（No. 81991501）、口腔疾病研究国家重点实验室开放课题基金（No. SKLOD2021OF03）和北京大学医学部与英国伦敦国王大学联合基金（No. BMU2020KCL003）资助

详细信息

通讯作者:
E-mail：chenfeng2011@hsc.pku.edu.cn

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出版历程
- 收稿日期: 2022-10-17
- 录用日期: 2023-02-21
- 修回日期: 2023-02-19
- 刊出日期: 2023-03-22

Relationship between Oral Microbiota and Alzheimer's Disease

1. Central Laboratory, School of Stomatology, Peking University, Beijing 100081, China
2. Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100083, China
3. Department of Biology, School of Stomatology, Peking University, Beijing 100081, China

More Information

Corresponding author: E-mail: koko体育app:chenfeng2011@hsc.pku.edu.cn

摘要

摘要: 阿尔茨海默症（Alzheimer’s disease, AD）是一种常见的神经退行性疾病。在老龄化社会中，AD的高患病率和低生活质量给个人、家庭和社会带来严重困扰，但AD的病因和致病机制并未完全明确，年龄、遗传、环境等因素都与之有关，治疗也没有令人满意的效果。最近有研究表示，口腔菌群失调与AD发病有密切关系，口腔细菌感染可能是引发AD的病因之一。口腔是人体最大的微生物生态系统，其稳态对健康至关重要。口腔菌群紊乱导致的细菌感染会通过直接和间接作用造成大脑内β-淀粉样蛋白（amyloid β-protein, Aβ）代谢失衡，Tau蛋白过磷酸化，沉积形成老年斑和神经原纤维缠结（neurofibrillary tangles, NFTs）损伤神经元。本文根据最新的研究进展，讨论口腔菌群与AD发生的相关性和机制，以及主要口腔细菌的致病机制，探索口腔菌群靶向疗法的潜在应用前景。
- koko体育app: 阿尔茨海默症 /
- 口腔菌群 /
- 神经炎症 /
- 牙龈卟啉单胞菌
Abstract: Alzheimer’s disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid β-protein (Aβ) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.
- Alzheimer's disease /
- koko体育app: Oral microbiota /
- koko体育app: Neuroinflammation /
- Porphyromonas gingivalis

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图 1 口腔菌群对脑组织的直接损伤作用

Figure 1. Dire🃏ct damage o💧f oral microflora to brain tissue
A: Some bacteria can directly produce Aβ precipitation accumulation in brain tissue; B: Microglia are continuously activated by bacteria and toxins entering brain tissue, releasing inflammatory factors and causing neuroinflammation; C: Bacteria and toxins activate the complement system; D: Inflammatory factors and complement fragments promote Aβ precipitation and Tau protein hyperphosphorylation; E: Aβ precipitation and hyperphosphorylation of Tau protein stimulate microglia to produce inflammatory factors that maintain or exacerbate neuroinflammation; F: Excessive Aβ precipitation and hyperphosphorylated Tau protein damage neurons and induce AD. OMV: Outer membrane vesicle; LPS: Lipopolysaccharide; TNF: Tumor necrosis factor; Aβ: Amyloid β-protein; IL-1: Interleukin-1; IL-6: Interleukin-6; IL-12: Interleukin-12; IL-23: Interleukin-23.

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图 2 细菌、毒素和炎症因子通过BBB途径

Figure 2. Bacteria, toxins and inflaꦬmmatory factors pass through the BBB pathway
A: Destruction of BBB barrier cells; B: Activating barrier cells to secret nitric oxide (NO), prostaglandin (PG) and other signaling molecules, and promoting brain cells to produce inflammatory factors, such as LPS-stimulated IL-6; C: Cell-specific transporters transporting inflammatory factors, such as TNF transporters. OMV: Outer membrane vesicle; LPS: Lipopolysaccharide; TNF: Tumor necrosis factor; IL-1: Interleukin-1; IL-6: Interleukin-6; BBB: Blood-brain barrier.

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